The present proposal will investigate the origin of fetal plasma dopamine and its possible physiological functions during fetal life. It is based on our studies with rat, sheep and human fetuses in which dopamine levels are 2-5 fold higher in fetal than in maternal or in non-pregnant adult plasma. Investigation will undertake three objectives: 1. To identify the source(s) of circulating dopamine in the fetus. It is assumed that the major source is the fetal para aortic bodies, but contributions from the adrenals, brain and the maternal circulation will also be investigated. Catecholamine concentration and dopamine beta hydroxylase activity will be measured by radioenzymatic assays in selected tissues from rat fetuses from day 16 to 22 of gestation. Dopamine turnover will be studied after injections of alpha methyl para tyrosine. Possible placental transport of dopamine will be determined following injections of tritiated dopamine into the maternal circulation. 2. To determine the distribution and characteristics of dopaminergic receptors in peripheral tissues from rat and sheep fetuses. Receptor distribution will be determined by a whole body autoradiography and by tissue uptake of the tritiated dopaminergic receptor antagonist, spiroperidol. Binding affinities and receptor density in tissues identified in the above studies will be measured in vitro utilizing untreated fetal tissue homogenates. 3. To study the dynamics of fetal plasma dopamine, its interactions with prolactin and glucocorticoids and its response to hypoxia. Catecholamines, prolactin and cortisol will be determined in plasma from chronically cannulated sheep fetuses at 4-5 day intervals from days 120 to 145 of gestation. Possible changes in fetal plasma dopamine levels will be studied following maternal or fetal adrenaloctomy or fetal adrenal demedullation. The effects of exposing pregnant ewes to hypoxia on circulating fetal plasma catecholamines will also be studied. This research will contribute to a better understanding of basic endocrine mechanisms during fetal life.